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1.
Int J Mol Sci ; 23(7)2022 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-35408861

RESUMEN

Lipid domains less than 200 nm in size may form a scaffold, enabling the concerted function of plasma membrane proteins. The size-regulating mechanism is under debate. We tested the hypotheses that large values of spontaneous monolayer curvature are incompatible with micrometer-sized domains. Here, we used the transition of photoswitchable lipids from their cylindrical conformation to a conical conformation to increase the negative curvature of a bilayer-forming lipid mixture. In contrast to the hypothesis, pre-existing micrometer-sized domains did not dissipate in our planar bilayers, as indicated by fluorescence images and domain mobility measurements. Elasticity theory supports the observation by predicting the zero free energy gain for splitting large domains into smaller ones. It also indicates an alternative size-determining mechanism: The cone-shaped photolipids reduce the line tension associated with lipid deformations at the phase boundary and thus slow down the kinetics of domain fusion. The competing influence of two approaching domains on the deformation of the intervening lipids is responsible for the kinetic fusion trap. Our experiments indicate that the resulting local energy barrier may restrict the domain size in a dynamic system.


Asunto(s)
Membrana Dobles de Lípidos , Modelos Químicos , Elasticidad , Cinética , Conformación Molecular
2.
Phys Rev Lett ; 124(10): 108102, 2020 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-32216409

RESUMEN

Lipid rafts serve as anchoring platforms for membrane proteins. Thus far they escaped direct observation by light microscopy due to their small size. Here we used differently colored dyes as reporters for the registration of both ordered and disordered lipids from the two leaves of a freestanding bilayer. Photoswitchable lipids dissolved or reformed the domains. Measurements of domain mobility indicated the presence of 120 nm wide ordered and 40 nm wide disordered domains. These sizes are in line with the predicted roles of line tension and membrane undulation as driving forces for alignment.


Asunto(s)
Lípidos de la Membrana/administración & dosificación , Microdominios de Membrana/química , Colesterol/química , Colesterol/metabolismo , Diglicéridos/química , Diglicéridos/metabolismo , Lípidos de la Membrana/química , Lípidos de la Membrana/metabolismo , Microdominios de Membrana/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Microscopía Confocal/métodos , Modelos Químicos , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Espectrometría de Fluorescencia/métodos
3.
Soft Matter ; 16(5): 1333-1341, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-31934706

RESUMEN

Archaea are prokaryotic microorganisms famous for their ability to adapt to extreme environments, including low and high temperatures. Archaeal lipids often are macrocycles with two polar heads and a hydrophobic core that contains methyl groups and in-line cycles. Here we present the design of novel general-purpose surfactants that have inherited features of archaeal lipids. These are C12 and C14 carboxylic acids containing in-line cyclopentanes. The cyclopentanes disturb the chain packing, which results in remarkable expansion of the operational range of the surfactant into the low-temperature region. We report synthesis and properties of these novel archaea-like surfactants and details of their chain packing derived from thermodynamics model predictions, molecular dynamics simulations, and experimental data on CMC and Krafft points.


Asunto(s)
Archaea/metabolismo , Ciclopentanos/química , Tensoactivos/química , Archaea/química , Ciclopentanos/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Metabolismo de los Lípidos , Lípidos/química , Simulación de Dinámica Molecular , Termodinámica
4.
Soft Matter ; 16(5): 1179-1189, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-31934707

RESUMEN

The theory of elasticity of lipid membranes is used widely to describe processes of cell membrane remodeling. Classically, the functional of a membrane's elastic energy is derived under assumption of small deformations; the membrane is considered as an infinitely thin film. This functional is quadratic on membrane surface curvature, with half of the splay modulus as its proportionality coefficient; it is generally applicable for small deformations only. Any validity of this functional for the regime of strong deformations should be verified experimentally. Recently, research using molecular dynamics simulations challenged the validity of this classic, linear model, i.e. the constancy of the splay modulus for strongly bent membranes. Here we demonstrate that the quadratic energy functional still can be applied for calculation of the elastic energy of strongly deformed membranes without introducing higher order terms with additional elastic moduli, but only if applied separately for each lipid monolayer. For cylindrical membranes, both classic and monolayerwise models yield equally accurate results. For cylindrical deformations we experimentally show that the elastic energy of lipid monolayers is additive: a low molecular weight solvent leads to an approximately twofold decrease in the membrane bending stiffness. Accumulation of solvent molecules in the inner monolayer of a membrane cylinder can explain these results, as the solvent partially prevents lipid molecules from splaying there. Thus, the linear theory of elasticity can be expanded through the range from weak to strong deformations-its simplicity and physical transparency describe various membrane phenomena.


Asunto(s)
Membrana Celular/química , Lípidos de la Membrana/química , Elasticidad , Membrana Dobles de Lípidos/química , Simulación de Dinámica Molecular , Solventes/química
5.
Soft Matter ; 16(13): 3216-3223, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32161934

RESUMEN

Archaeal lipids ensure unprecedented stability of archaea membranes in extreme environments. Here, we incorporate a characteristic structural feature of an archaeal lipid, the cyclopentane ring, into hydrocarbon chains of a short-chain (C12) phosphatidylcholine to explore whether the insertion would allow such a lipid (1,2-di-(3-(3-hexylcyclopentyl)-propanoate)-sn-glycero-3-phosphatidylcholine, diC12cp-PC) to form stable bilayers at room temperature. According to fluorescence-based assays, in water diC12cp-PC formed liquid-crystalline bilayers at room temperature. Liposomes produced from diC12cp-PC retained calcein for over a week when stored at +4 °C. diC12cp-PC could also form model bilayer lipid membranes that were by an order of magnitude more stable to electrical breakdown than egg PC membranes. Molecular dynamics simulation showed that the cyclopentane fragment fixes five carbon atoms (or four C-C bonds), which is compensated by the higher mobility of the rest of the chain. This was found to be the reason for the remarkable stability of the diC12cp-PC bilayer: restricted conformational mobility of a chain segment increases the membrane bending modulus (compared to a normal hydrocarbon chain of the same length). Here, higher stiffness practically does not affect the line tension of a membrane pore edge. Rather it makes it more difficult for diC12cp-PC to rearrange in order to line the edge of a hydrophilic pore; therefore, fewer pores are formed.


Asunto(s)
Archaea/química , Ciclopentanos/química , Interacciones Hidrofóbicas e Hidrofílicas/efectos de los fármacos , Fosfolípidos/química , Electricidad/efectos adversos , Membrana Dobles de Lípidos/efectos de la radiación , Liposomas/química , Liposomas/efectos de la radiación , Conformación Molecular/efectos de la radiación , Agua/química
6.
Int J Mol Sci ; 21(11)2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32485905

RESUMEN

Starting from fertilization, through tissue growth, hormone secretion, synaptic transmission, and sometimes morbid events of carcinogenesis and viral infections, membrane fusion regulates the whole life of high organisms. Despite that, a lot of fusion processes still lack well-established models and even a list of main actors. A merger of membranes requires their topological rearrangements controlled by elastic properties of a lipid bilayer. That is why continuum models based on theories of membrane elasticity are actively applied for the construction of physical models of membrane fusion. Started from the view on the membrane as a structureless film with postulated geometry of fusion intermediates, they developed along with experimental and computational techniques to a powerful tool for prediction of the whole process with molecular accuracy. In the present review, focusing on fusion processes occurring in eukaryotic cells, we scrutinize the history of these models, their evolution and complication, as well as open questions and remaining theoretical problems. We show that modern approaches in this field allow continuum models of membrane fusion to stand shoulder to shoulder with molecular dynamics simulations, and provide the deepest understanding of this process in multiple biological systems.


Asunto(s)
Membrana Celular/fisiología , Membrana Dobles de Lípidos/química , Fusión de Membrana , Simulación de Dinámica Molecular , Animales , Elasticidad , Humanos , Modelos Biológicos , Distribución Normal
7.
Bioconjug Chem ; 30(4): 1098-1113, 2019 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-30817133

RESUMEN

Enzyme-responsive liposomes release their cargo in response to pathologically increased levels of enzymes at the target site. We report herein an assembly of phospholipase A2-responsive liposomes based on colchicinoid lipid prodrugs incorporated into lipid bilayer of the nanosized vesicles. The liposomes were constructed to addresses two important issues: (i) the lipid prodrugs were designed to fit the structure of the enzyme binding site; and (ii) the concept of lateral pressure profile was used to design lipid prodrugs that introduce almost no distortions into the lipid bilayer packing, thus ensuring that corresponding liposomes are stable. The colchicinoid agents exhibit antiproliferative activity in subnanomolar range of concentrations.


Asunto(s)
Colchicina/química , Liposomas , Fosfolípidos/química , Profármacos/química , Fenómenos Biofísicos , Proliferación Celular/efectos de los fármacos , Colchicina/farmacología , Fluoresceínas/química , Humanos , Membrana Dobles de Lípidos , Fosfolipasas A2/metabolismo
8.
Biophys J ; 115(3): 478-493, 2018 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-30049405

RESUMEN

Gramicidin A (gA) is a short ß-helical peptide known to form conducting channels in lipid membranes because of transbilayer dimerization. The gA conducting dimer, being shorter than the lipid bilayer thickness, deforms the membrane in its vicinity, and the bilayer elastic energy contributes to the gA dimer formation energy. Likewise, membrane incorporation of a gA monomer, which is shorter than the lipid monolayer thickness, creates a void, thereby forcing surrounding lipid molecules to tilt to fill it. The energy of membrane deformation was calculated in the framework of the continuum elasticity theory, taking into account splay, tilt, lateral stretching/compression, Gaussian splay deformations, and external membrane tension. We obtained the interaction energy profiles for two gA monomers located either in the same or in the opposite monolayers. The profiles demonstrated the long-range attraction and short-range repulsion behavior of the monomers resulting from the membrane deformation. Analysis of the profile features revealed conditions under which clusters of gA monomers would not dissipate because of diffusion. The calculated dependence of the dimer formation and decay energy barriers on the membrane elastic properties was in good agreement with the available experimental data and suggested an explanation for a hitherto contentious phenomenon.


Asunto(s)
Membrana Celular/química , Elasticidad , Gramicidina/química , Membrana Dobles de Lípidos/química , Multimerización de Proteína , Probabilidad , Estructura Cuaternaria de Proteína
9.
Int J Mol Sci ; 19(5)2018 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-29772704

RESUMEN

Sphingomyelin- and cholesterol- enriched membrane domains, commonly referred to as "rafts" play a crucial role in a large number of intra- and intercellular processes. Recent experiments suggest that not only the volumetric inhomogeneity of lipid distribution in rafts, but also the arrangement of the 1D boundary between the raft and the surrounding membrane is important for the membrane-associated processes. The reason is that the boundary preferentially recruits different peptides, such as HIV (human immunodeficiency virus) fusion peptide. In the present work, we report a theoretical investigation of mechanisms of influence of the raft boundary arrangement upon virus-induced membrane fusion. We theoretically predict that the raft boundary can act as an attractor for viral fusion peptides, which preferentially distribute into the vicinity of the boundary, playing the role of 'line active components' of the membrane ('linactants'). We have calculated the height of the fusion energy barrier and demonstrated that, in the case of fusion between HIV membrane and the target cell, presence of the raft boundary in the vicinity of the fusion site facilitates fusion. The results we obtained can be further generalized to be applicable to other enveloped viruses.


Asunto(s)
Infecciones por VIH/virología , VIH-1/fisiología , Fusión de Membrana , Microdominios de Membrana/metabolismo , Internalización del Virus , Algoritmos , Membrana Celular/química , Membrana Celular/metabolismo , Humanos , Modelos Biológicos
10.
Biophys J ; 112(2): 339-345, 2017 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-28122219

RESUMEN

Phase separation in biological membranes plays an important role in protein targeting and transmembrane signaling. Its occurrence in both membrane leaflets commonly gives rise to matching liquid or liquid-ordered domains in the opposing monolayers. The underlying mechanism of such co-localization is not fully understood. The decrease of the line tension around the thicker ordered domain constitutes an important driving force. Yet, robust domain coupling requires an additional energy source, which we have now identified as thermal undulations. Our theoretical analysis of elastic deformations in a lipid bilayer shows that stiffer lipid domains tend to distribute into areas with lower fluctuations of monolayer curvature. These areas naturally align in the opposing monolayers. Thus, coupling requires both membrane leafs to display a heterogeneity in splay rigidities. The heterogeneity may either originate from intrinsic lipid properties or be acquired by adsorption of peripheral molecules. Undulations and line tension act synergistically: the gain in energy due a minimized line tension is proportional to domain radius and thus primarily fuels the registration of smaller domains; whereas the energetic contribution of undulations increases with membrane area and thus primarily acts to coalesce larger domains.


Asunto(s)
Membrana Celular/química , Membrana Celular/metabolismo , Modelos Biológicos
11.
Int J Mol Sci ; 18(12)2017 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-29207481

RESUMEN

Fusion of cellular membranes during normal biological processes, including proliferation, or synaptic transmission, is mediated and controlled by sophisticated protein machinery ensuring the preservation of the vital barrier function of the membrane throughout the process. Fusion of virus particles with host cell membranes is more sparingly arranged and often mediated by a single fusion protein, and the virus can afford to be less discriminative towards the possible different outcomes of fusion attempts. Formation of leaky intermediates was recently observed in some fusion processes, and an alternative trajectory of the process involving formation of π-shaped structures was suggested. In this study, we apply the methods of elasticity theory and Lagrangian formalism augmented by phenomenological and molecular geometry constraints and boundary conditions to investigate the traits of this trajectory and the drivers behind the choice of one of the possible scenarios depending on the properties of the system. The alternative pathway proved to be a dead end, and, depending on the parameters of the participating membranes and fusion proteins, the system can either reversibly enter the corresponding "leaky" configuration or be trapped in it. A parametric study in the biologically relevant range of variables emphasized the fusion protein properties crucial for the choice of the fusion scenario.


Asunto(s)
Membrana Celular/química , Fusión de Membrana , Proteínas Virales de Fusión/metabolismo , Internalización del Virus , Algoritmos , Animales , Membrana Celular/fisiología , Elasticidad , Humanos , Modelos Biológicos , Proteínas Virales de Fusión/química , Virus/química
12.
Langmuir ; 32(6): 1591-600, 2016 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-26783730

RESUMEN

7-Dehydrocholesterol, an immediate metabolic predecessor of cholesterol, can accumulate in tissues due to some metabolic abnormalities, causing an array of symptoms known as Smith-Lemli-Opitz syndrome. Enrichment of cellular membranes with 7-dehydrocholesterol interferes with normal cell-signaling processes, which involve interaction between rafts and formation of the so-called signaling platforms. In model membranes, cholesterol-based ordered domains usually merge upon contact. According to our experimental data, ordered domains in the model systems where cholesterol is substituted for 7-dehydrocholesterol never merge on the time scale of the experiment, but clusterize into necklace-like aggregates. We attribute such different dynamical behavior to altered properties of the domain boundary. In the framework of thickness mismatch model, we analyzed changes of interaction energy profiles of two approaching domains caused by substitution of cholesterol by 7-dehydrocholesterol. The energy barrier for domain merger is shown to increase notably, with simultaneous appearance of another distinct local energy minimum. Such energy profile is in perfect qualitative agreement with the experimental observations. The observed change of domain dynamics can impair proper interaction between cellular rafts underlying pathologies associated with deviations in cholesterol metabolism.


Asunto(s)
Deshidrocolesteroles/química , Microdominios de Membrana/química , Colesterol/química , Elasticidad , Modelos Químicos , Fosfatidilcolinas/química , Esfingomielinas/química , Liposomas Unilamelares/química
13.
Soft Matter ; 12(8): 2357-64, 2016 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-26791255

RESUMEN

Archaeal membranes have unique mechanical properties that enable these organisms to survive under extremely aggressive environmental conditions. The so-called bolalipids contribute to this exceptional stability. They have two polar heads joined by two hydrocarbon chains. The two headgroups can face different sides of the membrane (O-shape conformation) or the same side (U-shape conformation). We have developed an elasticity theory for bolalipid membranes and show that the energetic contributions of (i) tilt deformations, (ii) area compression/stretching deformations, (iii) as well as those of Gaussian splay from the two membrane surfaces are additive, while splay deformations yield a cross-term. The presence of a small fraction of U-shaped molecules resulted in spontaneous membrane curvature. We estimated the tilt modulus to be approximately equal to that of membranes in eukaryotic cells. In contrast to conventional lipids, the bolalipid membrane possesses two splay moduli, one of which is estimated to be an order of magnitude larger than that of conventional lipids. The projected values of elastic moduli act to hamper pore formation and to decelerate membrane fusion and fission.


Asunto(s)
Membrana Celular/química , Membrana Dobles de Lípidos/química , Elasticidad , Modelos Moleculares
14.
Phys Rev Lett ; 115(8): 088101, 2015 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-26340212

RESUMEN

The mechanism responsible for domain registration in two membrane leaflets has thus far remained enigmatic. Using continuum elasticity theory, we show that minimum line tension is achieved along the rim between thicker (ordered) and thinner (disordered) domains by shifting the rims in opposing leaflets by a few nanometers relative to each other. Increasing surface tension yields an increase in line tension, resulting in larger domains. Because domain registration is driven by lipid deformation energy, it does not require special lipid components or interactions at the membrane midplane.


Asunto(s)
Lípidos de la Membrana/química , Modelos Biológicos , Modelos Químicos , Membrana Celular/química , Membrana Celular/metabolismo , Colesterol/química , Colesterol/metabolismo , Elasticidad , Lípidos de la Membrana/metabolismo , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Tensión Superficial , Termodinámica
15.
ACS Infect Dis ; 10(8): 2870-2885, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-38917054

RESUMEN

Human immunodeficiency virus (HIV) assembly at an infected cell's plasma membrane requires membrane deformation to organize the near-spherical shape of an immature virus. While the cellular expression of HIV Gag is sufficient to initiate budding of virus-like particles, how Gag generates membrane curvature is not fully understood. Using highly curved lipid nanotubes, we have investigated the physicochemical basis of the membrane activity of recombinant nonmyristoylated Gag-Δp6. Gag protein, upon adsorption onto the membrane, resulted in the shape changes of both charged and uncharged nanotubes. This shape change was more pronounced in the presence of charged lipids, especially phosphatidylinositol bisphosphate (PI(4,5)P2). We found that Gag modified the interfacial tension of phospholipid bilayer membranes, as judged by comparison with the effects of amphipathic peptides and nonionic detergent. Bioinformatic analysis demonstrated that a region of the capsid and SP1 domains junction of Gag is structurally similar to the amphipathic peptide magainin-1. This region accounts for integral changes in the physical properties of the membrane upon Gag adsorption, as we showed with the synthetic CA-SP1 junction peptide. Phenomenologically, membrane-adsorbed Gag could diminish the energetic cost of increasing the membrane area in a way similar to foam formation. We propose that Gag acts as a surface-active substance at the HIV budding site that softens the membrane at the place of Gag adsorption, lowering the energy for membrane bending. Finally, our experimental data and theoretical considerations give a lipid-centric view and common mechanism by which proteins could bend membranes, despite not having intrinsic curvature in their molecular surfaces or assemblies.


Asunto(s)
Membrana Celular , VIH-1 , Ensamble de Virus , Productos del Gen gag del Virus de la Inmunodeficiencia Humana , VIH-1/fisiología , VIH-1/química , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/química , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/metabolismo , Membrana Celular/química , Humanos , Membrana Dobles de Lípidos/química , Tensoactivos/química , Tensoactivos/farmacología , Nanotubos/química
16.
Phys Rev E ; 107(2-1): 024414, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36932616

RESUMEN

Many cellular processes such as endocytosis, exocytosis, and vesicle trafficking involve membrane deformations, which can be analyzed in the framework of the elastic theories of lipid membranes. These models operate with phenomenological elastic parameters. A connection between these parameters and the internal structure of lipid membranes can be provided by three-dimensional (3D) elastic theories. Considering a membrane as a 3D layer, Campelo et al. [F. Campelo et al., Adv. Colloid Interface Sci. 208, 25 (2014)10.1016/j.cis.2014.01.018] developed a theoretical basis for the calculation of elastic parameters. In this work we generalize and improve this approach by considering a more general condition of global incompressibility instead of local incompressibility. Crucially, we find an important correction to the theory of Campelo et al., which if not taken into account leads to a significant miscalculation of elastic parameters. With the total volume conservation taken into account, we derive an expression for the local Poisson's ratio, which determines how the local volume changes upon stretching and permits a more precise determination of elastic parameters. Also, we substantially simplify the procedure by calculating the derivatives of the moments of the local tension with respect to stretching instead of calculating the local stretching modulus. We obtain a relation between the Gaussian curvature modulus as a function of stretching and the bending modulus, showing that these two elastic parameters are not independent, as was previously assumed. The proposed algorithm is applied to membranes composed of pure dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and their mixture. The following elastic parameters of these systems are obtained: the monolayer bending and stretching moduli, spontaneous curvature, neutral surface position, and local Poisson's ratio. It is shown that the bending modulus of the DPPC/DOPC mixture follows a more complex trend than predicted by the classical Reuss averaging, which is often employed in theoretical frameworks.

17.
Membranes (Basel) ; 13(8)2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37623783

RESUMEN

Lateral transport and release of protons at the water-membrane interface play crucial roles in cell bioenergetics. Therefore, versatile techniques need to be developed for investigating as well as clarifying the main features of these processes at the molecular level. Here, we experimentally measured the kinetics of binding of protons released from the photoactivated compound sodium 2-methoxy-5-nitrophenyl sulfate (MNPS) at the surface of a bilayer lipid membrane (BLM). We developed a theoretical model of this process describing the damage of MNPS coupled with the release of the protons at the membrane surface, as well as the exchange of MNPS molecules and protons between the membrane and solution. We found that the total change in the boundary potential difference across the membrane, ∆ϕb, is the sum of opposing effects of adsorption of MNPS anions and release of protons at the membrane-water interface. Steady-state change in the ∆ϕb due to protons decreased with the concentration of the buffer and increased with the pH of the solution. The change in the concentration of protons evaluated from measurements of ∆ϕb was close to that in the unstirred water layer near the BLM. This result, as well as rate constants of the proton exchange between the membrane and the bulk solution, indicated that the rate-limiting step of the proton surface to bulk release is the change in the concentration of protons in the unstirred layer. This means that the protons released from MNPS remain in equilibrium between the BLM surface and an adjacent water layer.

18.
Membranes (Basel) ; 13(1)2023 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-36676883

RESUMEN

Topological rearrangements of biological membranes, such as fusion and fission, often require a sophisticated interplay between different proteins and cellular membranes. However, in the case of fusion proteins of enveloped viruses, even one molecule can execute membrane restructurings. Growing evidence indicates that matrix proteins of enveloped viruses can solely trigger the membrane bending required for another crucial step in virogenesis, the budding of progeny virions. For the case of the influenza A virus matrix protein M1, different studies report both in favor and against M1 being able to produce virus-like particles without other viral proteins. Here, we investigated the physicochemical mechanisms of M1 membrane activity on giant unilamellar vesicles of different lipid compositions using fluorescent confocal microscopy. We confirmed that M1 predominantly interacts electrostatically with the membrane, and its ability to deform the lipid bilayer is non-specific and typical for membrane-binding proteins and polypeptides. However, in the case of phase-separating membranes, M1 demonstrates a unique ability to induce macro-phase separation, probably due to the high affinity of M1's amphipathic helices to the raft boundary. Thus, we suggest that M1 is tailored to deform charged membranes with a specific activity in the case of phase-separating membranes.

19.
Membranes (Basel) ; 12(10)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36295751

RESUMEN

Lipid droplets are unique organelles that store neutral lipids encapsulated by the lipid monolayer. In some processes of cellular metabolism, lipid droplets interact with peroxisomes resulting in the fusion of their envelopes and the formation of protrusions of the peroxisome monolayer, called pexopodia. The formation of pexopodia is facilitated by free fatty acids generated during lipolysis within lipid droplets. In this work, we studied the fusion of monolayer and bilayer membranes during the interaction between lipid droplets and peroxisomes. To this end, we built the energy trajectory of this process using the continuum elasticity theory and investigated the molecular details of the fusion structures utilizing molecular dynamics. We divided the fusion process into two stages: formation of a stalk and its consequent expansion into pexopodia. We found that in the considered system, the stalk was energetically more stable and had a lower energy barrier of formation compared to the case of bilayer fusion. The further evolution of the stalk depended on the value of the spontaneous curvature of the membrane in a threshold manner. We attributed the possible expansion of the stalk to the incorporation of free fatty acids into the stalk region. The developed model allowed describing quantitatively the process of monolayer-bilayer fusion.

20.
Front Mol Biosci ; 9: 1021321, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36275621

RESUMEN

The lipid matrix of cellular membranes, directly and indirectly, regulates many vital functions of the cell. The diversity of lipids in membranes leads to the formation of ordered domains called rafts, which play a crucial role in signal transduction, protein sorting and other cellular processes. Rafts are believed to impact the development of different neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's ones, amyotrophic lateral sclerosis, some types of cancer, etc. These diseases correlate with the change in the membrane lipid composition resulting from an oxidative stress, age-related processes, dysfunction of proteins, and many others. In particular, a lot of studies report a significant rise in the level of lysolipids. Physicochemical properties of rafts are determined by membrane composition, in particular, by the content of lysolipids. Lysolipids may thus regulate raft-involving processes. However, the exact mechanism of such regulation is unknown. Although studying rafts in vivo still seems to be rather complicated, liquid-ordered domains are well observed in model systems. In the present study, we used atomic force microscopy (AFM) to examine how lysophospholipids influence the liquid-ordered domains in model ternary membranes. We demonstrated that even a small amount of lysolipids in a membrane significantly impacts domain size depending on the saturation of the lysolipid hydrocarbon tails and the amount of cholesterol. The mixture with the bigger relative fraction of cholesterol was more susceptible to the action of lysolipids. This data helped us to generalize our previous theoretical model of the domain size regulation by lipids with particular molecular shape expanding it to the case of lysolipids and dioleoylglycerol.

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